Control of the EBV growth transformation programme: the importance of the Bamhi W repeats

Abstract

Epstein-Barr virus (EBV), a human gammaherpesvirus, possesses a unique set of latent genes whose constitutive expression in B cells leads to cell growth transformation. The initiation of this B-cell growth transformation programme depends on the activation of a viral promoter, Wp, present in each tandemly arrayed BamHI W repeat of the EBV genome. In order to examine the role of the BamHI W region in B cell infection and growth transformation, we constructed a series of recombinant EBVs carrying different numbers of BamHI W repeats and carried out B cell infection experiments. We concluded that EBV requires at least 2 copies of BamHI W repeats to be able to activate transcription and transformation in resting B cells in vitro. At least 5 copies of BamHI W were required for optimal transcription and transformation; while increasing the number beyond 5 copies had no further effect. Experiments to try to rescue the impaired virus indicated that the expression of sufficient levels of EBNA-LP and EBNA2 from Wp are the key determinants of virus-driven B cell transformation. We believe that EBV has evolved to contain multiple copies of BamHI W repeats to ensure high levels of Wp-initiated transcripts immediately post infection.

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